Apparatus for performing tests and measurements on liquid samples

ABSTRACT

An apparatus for performing tests and measurements on liquid samples comprises three identical juxtaposed stationary trays each provided with a plurality of receptacles for the samples to be examined. The receptacles are integrally molded in the trays. The receptacles of the first tray serve as storage vessels for the samples, and the receptacles of the two other trays serve as processing vessels. Three stations arranged above the trays and displaceable with respect to the same in a horizontal plane serve for transferring the samples from the first tray to the second and the third tray, for adding reagents and for discharging the reaction products from the receptacles of the second and the third tray. Each of the stations comprises a carriage displaceable over the trays in an X-direction and a hollow needle for injecting and removing liquids supported by the carriage and displaceable with respect to the same in an Y-direction perpendicular to the X-direction. The carriages and the needles are driven by associated belts, each adapted to be displaced by an associated drum driven by a D.C. motor. The arrangement of the belts and the dimensions of the drums are such that the movement of a needle in one of the said directions does not involve a movement in the other direction, and that each carriage and each needle may be displaced through its entire range by one revolution of the associated drum.

This is a continuation, of application Ser. No. 895,389, filed Apr. 11,1978 now U.S. Pat. No. 4,224,278.

BACKGROUND OF THE INVENTION

The invention relates to an apparatus for performing tests andmeasurements on various liquid samples, in particular sera.

A known apparatus of this kind comprises a first chain conveyorcontaining a series of receptacles. Indefinite quantities of the samplesto be tested are each introduced into one of these receptacles. Thereceptacles are led by the conveyor through a first station in which adefinite quantity of each sample is transferred to a second conveyoralso provided with a series of receptacles. Usually, a buffer reagent isadded to each sample during the transfer. The second conveyor may alsobe a chain conveyor, or it may be a rotatable disc. The receptacles ofthe second conveyor are led through a second station in which a startingreagent is added to each sample, after which the receptacles are ledthrough a third station, in which the reaction mixture in eachreceptacle is either removed by suction to be measured, or directlymeasured in its receptacle, according to the construction of thereceptacles.

The known apparatus has the disadvantage that the samples may not beintroduced into the first conveyor in an arbitrary order. In fact, thesamples to be subjected to a same measurement must be placed one behindthe other in the first conveyor. In addition, the known apparatus takesup much space.

BRIEF SUMMARY OF THE INVENTION

It is an object of the invention to provide an apparatus of theabove-mentioned kind, into which the samples may be introduced in anydesired order.

It is a further object of the invention to provide an apparatus of theabove-mentioned kind which may accommodate a large number of samples persurface unit.

For this purpose, the apparatus according to the invention ischaracterized by three identical juxtaposed trays each provided with aplurality of receptacles, the receptacles of the first tray serving asstorage vessels for the samples, and the receptacles of the second andthe third tray serving as processing vessels, and by three stationsarranged above the trays and displaceable with respect to the same in ahorizontal plane, the said stations serving for transferring the samplesfrom the receptacles of the first tray to those of the second or thethird tray, for adding reagents, and for discharging the reactionproducts, respectively.

In the apparatus according to the invention, the samples on the firsttray may be reached by the first station in any desired order, so thatthe samples need not be arranged in the first tray in a prescribedorder. Also, the apparatus only takes up a relatively small space.

In a preferred embodiment of the invention, each of the said stationscomprises a carriage displaceable over the three trays in anX-direction, and a hollow needle for injecting or removing a liquid,supported by the carriage and displaceable with respect to the same inan Y-direction perpendicular to the X-direction. Thus, an accuratepositioning of the needles with respect to the receptacles may beobtained in a simple manner. The needles may be self-stirring.

Preferably, the displacement of each carriage in the X-direction and ofeach needle in the Y-direction is brought about by an associated belt,the driving arrangement for the needles being carried out in such mannerthat the displacement of a needle in one of the two directions does notinvolve a displacement in the other direction.

The belts for displacing the carriages and the drums may be driven byassociated identical drums, each coupled with an associated D.C. motorthrough a speed reducing transmission. This allows for an economicalseries manufacture of the drums. The driving arrangements for thecarriages and the needles may be constructed in such manner that adisplacement of a carriage through its entire range in the X-direction,or of a needle through its entire range in the Y-direction requires onlyone revolution of the associated drum.

BRIEF DESCRIPTION OF THE DRAWING

FIG. 1 shows a top view of an apparatus according to the invention,including the driving arrangement for the carriages.

FIG. 2 shows a similar view of the apparatus according to FIG. 1,including the driving arrangements for the needles.

FIG. 3 shows a schematic representation of the driving arrangement forthe carriages.

FIG. 4 shows a schematic representation of the driving arrangement forthe needles.

FIG. 5 shows a cross section along the line V--V in FIG. 1.

FIG. 6 shows a perspective view of a driving motor, including thevarious parts of the position control.

FIG. 7 shows a developed view of an axially extending edge of a drumprovided with a binary series code.

FIG.8a shows a diagram of the voltage produced by the photocell.

FIG. 8b shows a diagram of the associated motor voltage.

FIG. 9 shows an overall view of the apparatus as shown in the previousFigures.

DETAILED DESCRIPTION

In the following description it has been presumed that the apparatus isused for testing or measuring sera, i.e. blood samples of variouspatients that are to be subjected to different measurements. However, itwill be clear that the apparatus according to the invention can also beused for other tests and measurements on any liquid samples that are tobe examined in a laboratory.

The apparatus shown in FIGS. 1 and 2 comprises three stationary trays 1,2 and 3 mounted in a table 4, which may be moved up and down. Each traycomprises one hundred and twenty-eight receptacles 5 which areintegrally molded in the tray. The receptacles 5 of a tray 1 serve asstorage vessels for the sera, while the receptacles 5 of trays 2 and 3serve as processing vessels.

Three carriages 6, 7 and 8, supporting needles 9, 10 and 11,respectively, are arranged above the trays. The carriages are movableover the trays in an X-direction and the needles are movable withrespect to the carriages in an Y-direction perpendicular to theX-direction, so that any receptacle may be reached by the needles. Forthe sake of clarity FIG. 1 only shows the driving arrangement for thecarriages and FIG. 2 only shows the driving arrangement for the needles.The driving arrangements will be further explained hereinafter.

The carriage 6 with the needle 9 removes a definite quantity of a serumfrom a receptacle on tray 1 and transfers this serum to one of thereceptacles of tray 2 or 3. The serum is injected into the latterreceptacle together with a buffer reagent. The needle 9 performs astirring movement during the injection and during its removal from theliquid, so that no liquid drops remain attached to the needle when itleaves a receptacle. In addition, the serum is intimately mixed with thebuffer reagent. After the transfer of the serum carriage 6 returns toits starting position in which a cleaning device 12 is arranged. Theneedle 9 is rinsed in this cleaning device, after which a serum may beinjected in a next receptacle 5. If desired, a separate needle may beused for the buffer reagent.

After carriage 6 has injected a serum into a receptacle, carriage 7 mayadd after a predetermined time a starting reagent. After a predeterminedreaction time needle 11 of carriage 8 removes the mixture from thereceptacle to be photometrically examined by means of a flow cell or thelike.

The needles 10 and 11 of the carriages 7 and 8 also perform a stirringmovement during an injection and during the removal from the liquid inorder to prevent liquid drops from being attached. At the same time thestarting reagent is intimately mixed with the serum by needle 10. Acleaning device 13 has been provided for the needles 10 and 11, in whichthey are rinsed after each operation.

FIG. 5 shows that the trays 1, 2 and 3 are placed in carriers 26, 27 and28, respectively. The carriers consist of aluminum blocks which areheated to a desired temperature and maintained at the same by means ofPeltier elements 29, 30 and 31, which are arranged on a platform 37. Thecarriers 26, 27 and 28 are constructed in such manner that a goodcontact is obtained with the receptacles, so that the temperature of theliquid is substantially equal to the temperature of the block. Thecarriers 26, 27 and 28, the Peltier elements 29, 30 and 31, the platform37 and the table 4 constitute an assembly 52 which may be moved up anddown. By the upward movement of the assembly 52 the needles may beintroduced into the receptacles 5 or into the cleaning devices 12 and 13for the removal or injection of a serum, or for rinsing, respectively.The upward movement is provided by a motor which drives a pin 43,attached to the platform 37 by means of a disc 41 and a rod 42. Themotor needs only produce a slight force, because the weight of theassembly 52 is compensated for a major part by a spring 44 exerting aforce on the assembly 52 by means of a rod 45 and a pair of tumblers 46and 47. Because the fixed joinings 48 and 49 are in one horizontal linewith the hinges 50 and 51 coupling the tumblers 46 and 47 with theplatform 37, and because the total displacement is small, the movementof the assembly 52 will be a vertical translation.

The carriages are simultaneously moved to the left or to the right, sothat they do not interfere with each other. For instance, carriage 6 maybe in its starting position for cleaning purposes, while carriage 7 addsa starting reagent to a receptacle and carriage 8 removes a sample formeasuring purposes.

The first receptacle to be filled on tray 3 is indicated by 5'. Afterthat the receptacles are successively filled in the Y-direction. Whenall receptacles 5 of tray 3 have been filled, tray 2 is used for furtheroperation. The "distance" between carriages 6 and 8 may be, forinstance, at most one hundred and twenty receptacles. In this case it iscertain that carriage 8 operates on tray 2, when carriage 6 has filledall the receptacles of tray 2. The operation on tray 3 has been finishedat that time, so that it may be replaced by a new tray, on whichcarriage 6 may continue its operation, when all receptacles of tray 2have been filled.

The apparatus performs a series of measurements of a same kind directlyafter each other. For instance, if a measurement A has to be performedon fifty sera of tray 1, the carriage 6 transfers these sera to fiftysubsequent receptacles of tray 2 or 3. Since the needle 9 of carriage 6may reach the receptacles of tray 1 in any desired order, the sera neednot be placed in the receptacles of tray 1 in any prescribed order.

After the first series of measurements has been finished, a next seriesmay be started, for instance thirty measurements B. For this purpose thesera are transferred to the next thirty receptacles of tray 2 or 3.

The duration of a cycle, i.e. the time required for a completetreatment, such as rinsing, sucking up and injecting for carriage 6, maybe 15, 20, 25 or 30 seconds, so that for a maximum distance of onehundred and twenty receptacles between carriages 6 and 8 the followingincubation times are obtained between the injection of a serum togetherwith the buffer reagent and the measurement:

15 sec. up to 30 min., max. 240 measurements/h

20 sec. up to 40 min., max. 180 measurements/h

25 sec. up to 50 min., max. 144 measurements/h

30 sec. up to 60 min., max. 120 measurements/h

The moment at which the starting reagent is added may be selected withinthe above limits.

The carriages 6, 7 and 8 are provided at each end with three wheels 14running in a U-profile 15, so that the carriages may also move in theX-direction. The carriages and the needles are each driven by a D.C.motor by means of a belts. Motors A, B and C serve for the displacementof carriages 6, 7 and 8 in the X-direction, while motors D, E and Fserve for the displacement of the needles in the Y-direction. As appearsfrom FIG. 2, the needles are attached to needle carriers 38, 39 and 40,each running with three wheels 23 in a U-profile 24.

The driving arrangement for the X-direction is schematically shown inFIG. 3. A drum 16 is driven by the motor with a speed reduction of 1:36.The drum 16 displaces a belts 17 guided by rollers 18 and attached to acarriage with both ends. The circumference of drum 16 has been selectedin such manner that a complete displacement in the X-direction requiresone revolution of the drum.

The driving arrangement for the Y-direction is schematically shown inFIG. 4. A drum 19 displaces a belts 20 guided by rollers 21 and 22, ofwhich the rollers 22 are arranged on the carriage. The total path in theY-direction is half the total path in the X-direction. Due to thearrangement of the rollers as shown the length of the belts to bedisplaced for the Y-direction is twice the length to be displaced forthe X-direction. This makes it possible to use identical drums for bothmovements, so that a complete displacement in the Y-direction alsorequires only one revolution of the drum.

The motors for the movements in both directions are fixedly attached tothe apparatus. The driving arrangement as shown ensures that a movementin the X-direction does not involve the movement in the Y-direction andvice versa.

The needles are brought above the desired receptacles by means ofpositioners, each comprising a digital and an analogue portion. Thedigital positioning is performed stepwise by means of a binary seriescode provided in an axially extending edge 53 of the drum 16, as shownin FIG. 6. FIG. 7 shows a development of the edge 53. A completerevolution of drum 16 corresponds with 36 steps. A step is the distanceof a central position between two adjacent receptacles 5 to a centralposition between the two adjacent receptacles 5. Due to the speedreduction of 36:1 in the transmission 57 one step corresponds exactlywith one revolution of the motor shaft 54. The binary series code isconverted into electric signals by six light sources, cooperating withsix photocells (not shown in FIG. 6). The binary series code isconverted into an ordinary binary code, counting from 0 to 35 by aprogrammable permanent memory, so that the required position of a needlemay be determined in a simple manner.

As soon as the right code has been reached, the positioning is switchedover to the analogue portion. The required voltage is generated by aspiral disc 25 arranged on the motor shaft 54 and placed with its spiraledge in the path of a light beam thrown by a light source 55 on aphotocell 56. Thus, during each revolution of the motor shaft 54 theexposure of the photocell 56 increases from a minimum to a maximumvalue, so that the photocell 56 produces a sawtooth voltage as shown inFIG. 8a. By comparing this voltage with a reference voltage, of whichthe value lies between the minimum and the maximum of the sawtoothvoltage in a PD control unit, the accurate position of the motor shaft54 is obtained. Due to the differentiating action of the control unitthe shaft is strongly braked after the switch-over to the analogueportion, so that the needles does not overshoot but immediately reachesthe correct position above the receptacle 5. The voltage delivered bythe PD control unit to the motor is shown in FIG. 8b.

The positioning might also be obtained exclusively with the analogueportion by counting the number of cycles of the sawtooth voltage.However, the combination of a digital and an analogue operation has theadvantage that the accuracy and the reproduceability of each discretestep is high and independent of the number of steps.

The apparatus is provided with a photometer for performing themeasurements. The results may be indicated by a digital display 32and/or a printer 33 (FIG. 9).

Furthermore, the apparatus is provided with an operating key-board 34,an entering key-board 35 and a reading and writing device 36 formagnetic cards or tapes. By means of these provisions the apparatus mayreceive information required for the operation to be performed. Thecircuits for processing this information and for controlling thecarriages, the needles and the table may be carried out in the usualmanner.

Apart from the above described series of operations performed in theapparatus it is also possible to perform a part of these operationsoutside the apparatus. For instance, tray 2 or 3 may be filled andprepared by means of reagents outside the apparatus and introduced inthe apparatus after that, so that the apparatus only performs themeasurement.

The apparatus may be tested by introducing a checking serum into areceptacle of tray 2 or 3 by means of a pipette. After that the numberof the receptacle is inserted by hand, together with information aboutthe desired operations. Carriage 6 removes the required quantity of theserum and transfers it to another receptacle in which the sameoperations are performed as for a normal serum.

A serum blank, i.e. a serum with a buffer reagent and two portions ofdistilled water, may be obtained by removing a serum by means of theneedle 9 from a receptacle of tray 1 and injecting it together with abuffer reagent into another receptacle, and by adding to the latterreceptacle distilled water from a tank 59 instead of a starting reagent.

I claim:
 1. Apparatus for performing tests and measurements on variousliquid samples, in particular sera, comprising a plurality ofreceptacles for the samples to be examined, said receptacles serving asstorage and processing vessels for said samples, and further comprisinga plurality of stations arranged above said receptacles and means fordisplacing said stations with respect to said receptacles in alldirections in a horizontal plane, said stations serving for transferringsaid samples from a first receptacle to at least one second receptacle,for adding reagents, and for discharging reaction products from said atleast one second receptacle.
 2. Apparatus as claimed in claim 1 whereinsaid receptacles consist of recesses integrally molded into at least onetray.
 3. Apparatus as claimed in claim 1, wherein each of the saidstations comprises a carriage displaceable over the said receptacles inan X-direction, and a hollow needle for injecting or removing a liquidsupported by the associated carriage and displaceable with respect tothe same in an Y-direction perpendicular to said X-direction. 4.Apparatus as claimed in claim 3, further comprising means for subjectingeach of the said needles to a stirring movement during an injection, andduring its removal from a sample.
 5. Apparatus as claimed in claim 3,further comprising a first plurality of belts each adapted to drive oneof the said carriages in said X-direction, and a second plurality ofbelts each adapted to drive one of the said needles in said Y-direction,the belts of said second plurality being arranged in such manner that amovement of one of the said needles in one of the said directions doesnot involve a movement in the other one of the said directions. 6.Apparatus as claimed in claim 5, further comprising a plurality ofidentical drums each adapted to displace one of the said belts, aplurality of D.C. motors each associated with one of the said drums, anda plurality of speed reducing transmissions each coupling one of thesaid motors with the associated drum, the circumference of the saiddrums being selected in such manner that a displacement of one of thesaid carriages through its entire range in the X-direction, or adisplacement of one of the said needles through its entire range in theY-direction requires only one revolution of the associated drum. 7.Apparatus as claimed in claim 6, further comprising a plurality ofpositioners, each associated with one of the said drums and eachcomprising a discrete positioning portion and a linear positioningportion.
 8. Apparatus as claimed in claim 2 whereinsaid plurality ofreceptacles are positioned in a plurality of juxtaposed trays with saidstations arranged above said trays.
 9. Apparatus as claimed in claim 7,wherein said linear positioning portion of each of said positionerscomprises a spiral disc directly coupled with the associated motor, alight source protecting a light beam on the edge of said spiral disc, aphotocell cooperating with said light source to produce a sawtoothvoltage during each step of the associated discrete positioning portion,and a comparator comparing said sawtooth voltage with a fixed referencevoltage having a value between the maximum and minimum values of saidsawtooth voltage.
 10. Apparatus as claimed in claim 9, wherein each ofthe comparators associated with said needles comprises means adapted tosubstitute a sinusoidal voltage for said fixed reference voltage, so asto impart a stirring movement to the associated needle.
 11. Apparatus asclaimed in claim 1, further comprising a plurality of trays providedwith receptacles, a plurality of carriers each receiving one of saidtrays, and a plurality of Peltier elements each maintaining one of thesaid carriers at a predetermined temperature.
 12. Apparatus as claimedin claim 11, further comprising a common platform supporting saidcarriers, a plurality of cleaning devices for said needles supported bysaid platform, a plurality of water tanks associated with said cleaningdevices and supported by said platform, and means for imparting anupward movement to said platform in order to immerse said needles insaid receptacles and in said cleaning devices.
 13. Apparatus as claimedin claim 3, further comprising two fixed U-profiles extending in saidX-direction, wherein each of said carriages is provided with threewheels at one of its ends running in one of said U-profiles, and withthree wheels at its other end running in the other one of saidU-profiles.
 14. Apparatus as claimed in claim 3, wherein said pluralityof stations is three and further comprising three U-profiles eachattached to one of said carriages and each extending in saidY-direction, and three needle holders each associated with one of saidcarriages and supporting the associated needle, each of said needleholders being provided with three wheels running in the U-profileattached to the associated carrier.
 15. Apparatus as claimed in claim 1,further comprising a writing and reading device adapted to cooperatewith a magnetic information carrier, a printer, a digital display, andoperating key-board, and a key-board for entering the requiredinformation.
 16. Apparatus as claimed in claim 1, further comprising aflow cell photometer for measuring certain properties of said samples.17. Apparatus as claimed in claim 1, further comprising means on saidfirst station for adding a buffer reagent to each sample during itstransfer to a second receptacle.